tbuckley/cabot-search huggingface dataset:
Abstract 15324: The Fontan Circulation Shows Decreased Cell Survival and Oxidative Damage
Authors: Dipti Tripathi, Joiliana A Lecointe, Aihua Zhu, Shoko Ichimura, Katie Clouthier, Sushma Reddy
Journal: Circulation (2022)

Introduction: Single ventricle congenital heart disease such as hypoplastic left heart syndrome (HLHS) with a Fontan circulation accounts for the largest group of children hospitalized with circulation failure, with an in-hospital mortality of 20-50%. We sought to (i) evaluate the mechanisms underlying circulation failure and (ii) identify novel therapeutic targets. Methods: Blood was collected from patients with HLHS s/p Fontan and from controls with normal cardiac anatomy and function (N=5/group). Plasma microvesicles (MV) were isolated and proteomics assessed using data independent acquisition mass spectroscopy. Dysregulated proteins with a fold change &gt;1.5 or &lt; -1.5, p&lt;0.05 were evaluated using Ingenuity pathway analysis. Results: Age of Fontan patients vs. controls was 17.04±2 vs. 15.7±2.5, p=0.4; 20% were male in both groups. 60% of Fontan patients were in NYHA class II/III, 40% in NYHA class IV; 80% had Fontan-associated liver disease. Circulating MVs were released from cardiomyocytes, endothelial cells, and hepatocytes based on cell surface markers. Upregulated proteins (N=27) implicated cell death pathways (Solute carrier family 2, Angiotensinogen, CD14); while downregulated proteins (N=88) implicated impaired cell survival (tyrosine-protein kinase Yes, endothelial growth factors). MVs contained mitochondria and endoplasmic reticulum proteins implicating upregulation in reactive oxygen species signaling (catalase A, S100A8) and downregulation in antioxidant enzymes (GPX1, PRDX 5). Conclusion: Circulating MVs from patients with HLHS s/p Fontan are released from the heart, blood vessels, and liver providing a noninvasive signature of organ remodeling. The MV protein cargo implicates heightened cell death, oxidative damage and impaired cell survival, thereby providing insight into the mechanisms of Fontan associated circulation failure. Figure: Decreased Cell Survival and Oxidative Damage in the Fontan Circulation
Abstract 14706: Poor Medication Access as a Driver of Excess Heart Failure Readmissions in Deprived Neighborhoods
Authors: Apoorva Gangavelli, Zihao Liu, Jeffrey Wang, Alexis K Okoh, Rebecca Steinberg, Krishan Patel, Shivani Patel, Neal W Dickert, Alanna A Morris
Journal: Circulation (2022)

Background: Disparities in heart failure (HF) outcomes exist in the United States, in part, due to social determinants of health. Individuals from racial and ethnic minority groups report the highest rates of cost-related delays in care and worse access to high-quality medical therapy. We have previously demonstrated that individuals residing in more deprived neighborhoods experience higher readmissions, and Black patients are more likely to reside in deprived neighborhoods than White patients. Here, we engaged patients from the most deprived neighborhoods to understand drivers of excess readmission from the patient perspective. Methods: We conducted semi-structured in-depth interviews with 25 patients (mean age 61 ± 9 years, 96% Black, 40% female) readmitted with HF at Emory Healthcare hospitals, and living in a neighborhood in the top 10% of the Social Deprivation Index. Qualitative descriptive analysis of the interviews was performed using a multilevel coding strategy. Results: Patients in this cohort had a mean EF 39 ± 19%, and experienced 3.2 ± 2.5 readmissions in the preceding 12 months. Most patients (84%) highlighted lack of access to medications as a driver of hospital readmission. Representative quotes from individual patients are highlighted in the Table. Patients reported the etiology of their lack of medication access included medication costs (64%), only having access to re-fills through the emergency room or hospitalization (36%), low health literacy (12%), and limited access to transportation (8%). Conclusion: Lack of access to medications for patients with HF who live in socioeconomically deprived neighborhoods poses a challenge to reducing the burden of HF. Providing cost-effective and sustainable access to medications for patients with HF from low resource settings is a potential solution to decrease the number of HF hospitalization and readmissions in this vulnerable patient population.
Abstract 15675: Mid-Ventricular Hypertrophic Cardiomyopathy Presenting With Minoca
Authors: Alba Munoz Estrella, Alaleh Azhir, Yeraz Khachatoorian, Swiri Konje, Soheila Talebi
Journal: Circulation (2022)

Background: Mid-ventricular hypertrophic obstructive cardiomyopathy (HOCM) is an uncommon form of cardiomyopathy that is linked to an apical aneurysm, increasing the risk of sudden death. Cases: We described four patients who presented with chest pain or SOB. Troponin elevation, acute myocardial infarction on cardiac MRI and absence of obstructive coronary disease confirmed the diagnosis of MINOCA. Echo revealed a pressure gradient between the apical and basal chambers of the left ventricle. Cardiac MRI showed mid-ventricular HOCM and mid-cavity obliteration with akinetic apical chamber LGE revealed areas of sub-endocardial or transmural myocardial infarction at the level of obstruction and at the apical segments distal to the obstruction. The presence of myocardial edema on tissue mapping in the same area suggested acute myocardial injury (Figure). Discussion: The pathogenesis of development of apical myocardial scarring and aneurysm formation in mid-ventricular HOCM remains unknown. Other variant of hypertrophic cardiomyopathy shows mid-myocardial foci of scar inside the hypertrophied segments, indicating fibrosis. Whereas in our patients, the LGE revealed a sub-endocardial or transmural infarct (myocardial infarction pattern) - an uncommon pattern in other hypertrophic cardiomyopathy variants. This pattern and elevation of troponin during the acute phase of illness supports the hypothesis that apical aneurysm is due to apical myocardial ischemia in mid-ventricular HOCM. Tissue characterization and pattern of scar by cardiac MRI in these patients could be useful in understanding the pathophysiology of this type of HOCM.
Abstract 13194: Towards Understanding the Pathogenesis of Covid-19: Acute and Long-Term Mouse Models
Authors: Chenxiao Wang, Zheng Chen, joshua M currey, Robert V Blair, Nicholas J Maness, Jay Rappaport, Derek Pociask, Jay Kolls, Xuebin Qin
Journal: Circulation (2022)

SARS-CoV2 (CoV2) infection causes both acute and long-term health effects via damaging multiple organs including lung. The endothelial dysfunction associated with the infection may contribute to pathogenesis of acute COVID-19 and long COVID. However, the mechanisms underlying the endothelial dysfunction remain elusive. Development of mouse models for these diseases will help us better dissect these mechanisms and facilitate the development of therapeutics for treatment of the disease. Previously, we developed an acute COVID model by infecting human ACE2 transgenic (K18) mice with a lethal CoV2 dose. K18 mice developed severe COVID-19, including progressive body weight loss and fatality at days 7 post infection (DPI), severe lung interstitial inflammation, edema, hemorrhage, perivascular inflammation, systemic lymphocytopenia, and eosinopenia. We detected CoV2 in capillary endothelial cells, activation and adhesion of platelets and immune cells to the vascular wall of the alveolar septa, and increased complement deposition in the lungs in this model. These results indicate that CoV2 infection and infection-mediated immune activation caused endothelial dysfunction, which contributes to the pathogenesis of severe COVID-19. To further develop a model for long COVID, we infected K18 mice with sub lethal CoV2 dose, monitored the body weight and survival rate and characterized the lung and brain histological changes at 21 and 45 DPI. The infected mice progressively lost body weights from 5 to 7 DPI and started to rebound from 8 DPI and then returned to baseline at 13 DPI. Mice had extensive patchy inflammation in the lungs associated with collagen deposition and smooth muscle action expression. We also found moderate levels of total viral RNA in the lung but not brain while viral subgenomic RNA (a correlate of viral replication) was undetectable in lung or brain by qRT-PCR assay. Fluorescence staining showed co-localization of CoV2 spike protein and CD206 in lungs, suggesting macrophage engulfment CoV2 at late time points. Together, we have successfully established long-term COVID mouse models, which will be useful tools for further defining the role of endothelial dysfunction in pathogeneses of CoV2-related acute and long COVID.
Abstract 13050: Tirzepatide versus Semaglutide for Secondary Prevention of Major Adverse Cardiovascular Events in Patients Over the Age of 65 With Type 2 Diabetes Mellitus-Value per Money Analysis
Authors: Ronen Arbel, Ariel Hammerman, Enis Aboalhasan, Ben Sluckis, Joseph Azuri
Journal: Circulation (2022)

Introduction: Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) indicated to reduce major adverse cardiovascular events (MACE) in patients with Type 2Diabetes Mellitus (T2DM) and established cardiovascular disease (CVD). Tirzepatide is a novel GLP-1RA/GIP for the same purpose. Adding either agent to the standard of care may impose a significant economic burden on the healthcare system. Therefore, we compared their value for money for this indication in patients over 65. Hypothesis: Tirzepatide provides better value for money than semaglutide in reducing MACE in this age group. Methods: We calculated the cost needed to prevent one MACE with either drug by multiplying the annualized number needed to treat (NNT) to prevent one event by the annual cost of the therapy. Efficacy estimates were extracted from pre-specified subgroups of patients over 65 in relevant published randomized controlled trials. US drug costs were based on GoodRx prices as of June 2022. Results: The annualized NNT to prevent one MACE in patients over 65 with tirzepatide in SURPASS was 58 (95% CI: 36-∞) compared to 79 (95% CI: 45-∞) with semaglutide in SUSTAIN-6. The annual cost of tirzepatide is $12,678 versus $11,616 for semaglutide. Accordingly, the CNT to prevent one MACE with tirzepatide is $735,308 (95% CI: $456,398-∞) compared to $917,635 (95% CI: $522,703-∞) with semaglutide. Conclusions: Tirzepatide prescribed for secondary prevention of MACE in patients over 65 with T2DM and established CVD provides better value than semaglutide for the same purpose.
Abstract 13422: Sotagliflozin, a Dual SGLT-1/2 Inhibitor, Modulated Expression of Endothelial Proteins That Inhibit Reactive Oxygen Species During Inflammation Compared With Empagliflozin
Authors: Samuel Sherratt, Peter Libby, Deepak L Bhatt, Preston Mason
Journal: Circulation (2022)

Background: Reactive oxygen species (ROS) generated during endothelial cell (EC) dysfunction contributes to progression of atherosclerosis. The SGLT1/2 inhibitor sotagliflozin (sota) reduced atherothrombotic events and hospitalization for worsening heart failure in patients with diabetes (SCORED, SOLOIST). Unlike selective SGLT2 inhibitors, sotagliflozin significantly reduced ischemic events, including myocardial infarction and stroke. We compared the effects of sota and empagliflozin (empa) on expression of ROS signaling proteins in human vein ECs (HUVECs) challenged with interleukin-6 (IL-6) or lipopolysaccharide (LPS). Methods: HUVECs were treated with sota or empa (100 nM) for 30 minutes and the challenged with IL-6 (12 ng/mL) or LPS (100 ng/mL) for 24 hours. Global proteomic analysis was performed using LC/MS to measure relative expression levels of &gt;1,000 proteins. Only significant (p&lt;0.05) changes in expression between treatment groups &gt;1-fold were included in gene set enrichment analysis (GSEA) of biological pathways. Results: Sota significantly changed expression of 166 and 274 proteins in ECs challenged with IL-6 and LPS, respectively. Empa significantly modulated fewer proteins - 122 and 93 proteins - following challenge with IL-6 and LPS, respectively. GSEA revealed that sota, not empa, modulated proteins related to ROS detoxification within the “cellular response to oxidative stress” pathway (GO:0034599) compared to both IL-6 and LPS (pathway adjusted p-values = 0.0016 and 0.036, respectively). Within this pathway, sota increased expression of peroxiredoxin (PRDX) 5 and PRDX6 (1.2 and 1.1-fold) and glutathione peroxidase-1 (GPX1, 1.1-fold) relative to IL-6 alone. Relative to LPS, sota decreased expression GPX1 (1.2-fold), PRDX1 (1.1-fold), and increased thioredoxin (1.1-fold). None of these proteins were modulated significantly by empa. Conclusions: Sota significantly modulated expression of proteins linked to ROS detoxification and signaling in human ECs during inflammation compared to a selective SGLT2 inhibitor. These favorable effects of dual SGLT1/2 inhibition may have implications for inflammation and reduced atherothrombotic risk as demonstrated in outcome trials.
Abstract 14507: Perceptions and Attitudes About Advance Care Planning Among Healthcare Professionals of Cardiac Care: A Q Methodology Study
Authors: JinShil Kim, Hana Ko, Myoung Hwan Shin, Mi-seung Shin, Yoon Young Hwang, Mi Yeong Kim, KyungAh Cho, SeongHu Park, Hani Yi
Journal: Circulation (2022)

Background: Provision of advance care planning (ACP) in patients with cardiovascular diseases is suboptimal in South Korea, which leads to an increase in the burden of care. Healthcare professionals’ perspectives of ACP are particularly important to facilitate its utilization. However, Korean healthcare professionals’ perspectives on ACP remain unknown. Aim: We explored perspectives and attitudes regarding ACP among healthcare professionals (physicians and nurses) who provide care to patients with cardiovascular diseases, using a Q methodology. Methodology: The Q sample consisted of 40 statements representing perspectives for and attitudes toward ACP derived from a literature review, mass media reports, and an in-depth qualitative interview. P samples consisted of 10 physicians and 14 nurses. The P sample filled each grid with a statement in the Q sorting table. Data were analyzed using the PQ Method program. Results: Seventy-one percent of the variance was explained with four factors represented by 18 Q – sorters, with each variance explained by each factor ranging from 16% to 20%: Factor A (n=5), healthcare professional-led decision about ACP; Factor B (n=5), patient value-based persuasive decision about ACP; Factor C (n=5), prognosis-based passive support for ACP; Factor D (n=3), comprehensive consideration -induced decision for ACP. Six Q-sorters fell into either confounded or non-significant. Shared perspectives for ACP among Korean healthcare professionals emerged in areas including conceptual definition, educational support and training, and ethical and legal concerns, while each factor also presented unique and primary perspectives for ACP. Conclusions: Our research revealed shared and unique perspectives for ACP in Korean healthcare professionals who treat cardiac patients. The findings of this study provide basic data for the provision of ACP in which, as a major stakeholder, healthcare providers’ perspectives should be considered in educational support and training. Keywords: advance care planning; cardiac disease; nurse; physician; perspectives; Q methodology
Abstract 14605: Deleterious Effects of Type 2 Diabetes on the Myocardium of Patients With Aortic Stenosis
Authors: Maelle CHERPAZ, Gaultier SEILLIER, Cyrille Bergerot, Matteo Pozzi, Romain Pierrard, StÃ©phanie Chanon, Camille Brun, Lara Chalabreysse, Chloe May, Lucas Givre, Fadi Farhat, Marco Vola, Jean François Obadia, Camille Amaz, Melanie Paillard, Helene Thibault
Journal: Circulation (2022)

Introduction: Type 2 diabetes (T2D) may induce myocardial alterations and is associated with an increased risk of heart failure. T2D is often associated to LV pressure overload, as encountered in aortic stenosis (AS). Hypothesis: We hypothesized that T2D has deleterious effects on LV remodelling and function in patients with severe AS and we explored some underlying mechanisms. Methods: Non diabetic and T2D patients with severe AS, referred for aortic valve replacement, were included. Patients with atrial fibrillation, LV ejection fraction (LVEF) &lt;50%, significant coronaropathy or other valvulopathy were excluded. Before surgery, patients underwent blood tests and a complete echocardiography. During surgery, a LV myocardium biopsy was obtained for histological analysis. Results: We included 82 patients, including 33 T2D. Hypertension and dyslipidaemia were more frequent in T2D patients. Severity of the AS was similar between the two groups. Echocardiography revealed that T2D was associated with a more pronounced LV hypertrophy (mass LV 3D/hight 2.7 ; p=0.03) and systolic dysfunction (Global Longitudinal Strain (GLS) 15±3 vs 18±2 %; p&lt;0.01). In addition, LV ventricular filling pressure was more often increased in T2D patients (50% of T2D vs 26% of non-diabetics; p=0.03). Circulating levels of leptin and endothelin 1 were significantly higher in T2D. Interestingly leptin level correlates with diastolic function (left atrial strain; r=-0.25, p=0.01) and Endothelin 1 with LV mass (r=0.27, p&lt;0.001) and GLS. Histologic analysis revealed an enhanced cardiomyocyte hypertrophy in T2D biopsies but similar degrees of fibrosis. Proximity ligation assay displayed a significant decreased proximity between the IP3-receptor and the mitochondrial porin VDAC in T2D hearts suggesting a reduced reticulum-mitochondria Ca 2+ transfer. Conclusions: T2D is associated with an increased LV remodelling and dysfunction in patients with a severe AS as well as an increased circulating level of leptin and endothelin-1. Our results also suggest a potential role of reticulum-mitochondria Ca 2+ uncoupling.
Abstract 14891: Sudden Cardiac Arrest Manifesting With Pulseless Electrical Activity: Is There A “Sweet Spot” for Survival?
Authors: Lauri Holmstrom, Harpriya Chugh, Shiva Salmasi, Audrey Uy-Evanado, Chad Sorenson, Ziana Bhanji, Madison Seifer, Arayik S Sargsyan, Christopher Young, Sean Hurst, Angelo Salvucci, Jonathan Jui, Kyndaron Reinier, Sumeet S Chugh
Journal: Circulation (2022)

Introduction: The proportion of sudden cardiac arrests (SCA) manifesting with pulseless electrical activity (PEA) has increased significantly, and survival rate remains poor. However, a small PEA-SCA subgroup does survive and may yield key predictors of improved outcomes when compared to non-survivors. Aim: To identify clinical and resuscitation factors that predict survival from PEA-SCA. Methods: Our study sample is drawn from two ongoing community-based, prospective studies of out-of-hospital SCA. The Portland, OR metro area (Pop. approx. 1 million; 2002-2017) was used as a discovery population and Ventura County CA (Pop. approx. 850,000, 2015-2021) was the validation population. For the present sub-study, we included SCA cases with PEA as the presenting rhythm, who were resuscitated by EMS personnel. Results: In Oregon SUDS, we identified 1,057 PEA-SCA cases of which 105 (10%) survived to hospital discharge (STHD). The mean age of PEA cases was 68.4±15.8 years and 62% were male. In a multivariable model including resuscitation variables (age, sex, witnessed SCA, EMS response time, bystander CPR, public location), age (OR 0.98, 95% CI 0.97-0.99; p=0.001), male sex (OR 0.58, 95% CI 0.38-0.88; p=0.01), witnessed SCA (OR 3.0, 95% CI 1.7-5.3; p&lt;0001), and public location (OR 1.9, 95% CI 1.1-3.1; p=0.01) associated with STHD. In a multivariable model including clinical variables (age, sex, BMI, CAD, HF, CKD, DM, COPD, asthma), only age (OR 0.97, 95% CI 0.95-0.99; p=0.003) had an association with STHD. In Ventura PRESTO, we identified 695 PEA-SCA cases of which 82 (12%) were STHD. The mean age of PEA cases was 73.1±15.6 years and 63% were male. In a multivariable model including the same resuscitation variables, age (OR 0.97, 95% CI 0.95-0.98; p&lt;0.001) and public location (OR 3.6, 95% CI 1.7-7.6; p=0.001) associated with STHD. In a multivariable model including the same clinical characteristics, we found no significant predictors of STHD. Conclusions: Young age and cardiac arrest in a public location were the only independent predictors of survival from PEA-SCA in both discovery and validation populations. These findings suggest that enhancement of the community response to cardiac arrest may have the potential to improve survival outcomes in PEA-SCA.
Abstract 14836: Drug-Coated Balloon Angioplasty of <i>De Novo</i> Native Coronary Arteries Allows Favorable Vessel Healing With Regards to Vasomotor Function
Authors: Sunwon Kim
Journal: Circulation (2022)

Background: Pre-stent era witnessed the presence of abnormal vasomotion at balloon-injured coronary segments, leading to fatal vasospasm. Drug-coated balloon (DCB) angioplasty is fundamentally the same procedure that was performed in the pre-stent era, except for antiproliferative drug being delivered. We evaluated whether de novo native coronary lesions treated using DCB are prone to vasospasm and how they respond to ergonovine and nitrate. Methods and Results: Among 132 DCB angioplasty recipients, 89 patients underwent ergonovine provocation test at 6-9 months follow-up. Within-subject ergonovine- and nitrate-induced diameter changes were compared among the three different sites: DCB-treated vs. angiographically normal vs. segment showing prominent vasoreactivity (spastic). None of 132 patient experienced clinically refractory vasospastic angina during follow-up. Ergonovine induced vasospasm in seven patients; all cases were multifocal spasms either involving(n=2) or sparing DCB-treated segments(n=5). No patient showed focal spasms that exclusively involved DCB-treated lesions. Among patients with vasospastic features, DCB-treated segments showed less vasoconstriction than did the spastic counterparts (p&lt;0.001). 35.5% of DCB-treated segments showed constrictor-resistance during ergonovine provocation. A total of 274 segments including 110 DCB-treated lesions were analyzed to assess vasomotor function. Most of the analyzed segments were constricted and dilated significantly after ergonovine and nitrate administration (both, p&lt;0.001). Vasomotor function, defined as a combined constrictor and dilator response, was comparable between DCB-treated and angiographically normal segments (p=0.173), while significant differences were observed against spastic counterparts (p&lt;0.001). Conclusions: DCB-treated lesions were not vulnerable to vasospasm and some segments showed rather spasm-resistance. DCB angioplasty allowing favorable vessel healing facilitated restoration of vasomotor function achieving level comparable to angiographically normal segments as early as 6 months after index procedure. This study supports the safety of DCB-only strategy in treating de novo native coronary lesions.